Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
  • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
  • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
  • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
  • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
  • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
  • B01J31/189—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
  • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
  • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
  • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
  • B01J2231/60—Reduction reactions, e.g. hydrogenation
  • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
  • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
  • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
  • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
  • B01J2531/82—Metals of the platinum group
  • B01J2531/821—Ruthenium
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
  • C07B2200/07—Optical isomers
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C2601/00—Systems containing only non-condensed rings
  • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
  • C07C2601/14—The ring being saturated

Definitions

• the present invention relates to chiral ruthenium complexes of the general formula (I) RuX 1 X 2 L 1 L 2 (I) with a chiral ligand L 2 , which are suitable for the enantioselective transfer hydrogenation of prochiral ketones.
• catalytically active complexes In addition to catalytic hydrogenation with hydrogen, enantioselective transfer hydrogenation in the presence of chiral rhodium and ruthenium complexes is common.
• the catalytically active complexes generally also contain diphosphine ligands which are difficult to produce. In addition, only a moderate enantiomeric excess can be achieved using these complexes. For example, Genêt et al. (Synlett 1993, 478) a ruthenium complex with a chiral diphosphine ligand, which at best yields an enantiomeric excess of 62% (ee) in the transfer hydrogenation of acetophenone.
• the object of the invention is therefore to provide a better catalyst for the transfer hydrogenation of prochiral ketones.
• the catalyst should be easily accessible, ensure high enantioselectivity and be useful for the reduction of all types of ketones.
• alkyl means a straight-chain or branched alkyl group with preferably 1 to 6 and in particular 1 to 4 carbon atoms.
• alkyl groups are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl and t-butyl.
• Cycloalkyl preferably means C 5 -C 8 cycloalkyl and in particular cyclopentyl and cyclohexyl.
• Aromatic or aryl represents benzene, naphthalene or phenyl, ⁇ - or ⁇ -naphthyl.
• C 1 -C 4 alkyl-substituted aromatics are, for example, toluene, mesitylene or p-cymene.
• the heteroaryl groups are preferably 5- or 6-membered heteroaromatics with one or two nitrogen atoms, which may contain further aromatics condensed on. Examples are pyrrolyl, imidazolyl, pyridyl, pyrimidyl, indolyl, quinolinyl etc.
• An aralkyl or heteroaralkyl group represents a monovalent radical in which a C 1 -C 4 alkylene chain carries an aryl or heteroaryl group.
• Acyl represents RCO, where R in particular represents H or C 1 -C 4 alkyl.
• the C 1 -C 10 carboxylic acids whose anions can be used as ligand X 1 or X 2 in the complex according to the invention are linear or branched alkane carboxylic acids which may have 1, 2 or 3 chlorine or fluorine atoms or corresponding ones Derivatives of benzoic acid or naphthoic acid.
• Preferred Complexes are those in which X 1 or X 2 independently of one another represent halide, in particular chloride, bromide and / or iodide or the anion of a C 1 -C 4 -carboxylic acid, in particular acetate, propionate and / or butyrate.
• X 1 and X 2 together can represent the dianion of a 1,3-, 1,4- or 1,5-dicarboxylic acid. This includes derivatives of malonic acid, succinic acid or glutaric acid.
• Preferred ligands L 1 in the complexes according to the invention having the formula (I) are CO, PF 3 and 1,5-cyclooctadiene and phosphine ligands of the general formula (II) in which the groups R 1 , R 2 and R 3 are preferably, independently of one another, for linear or branched C 1 -C 4 alkyl groups or phenyl groups which are optionally substituted by 1, 2 or 3 C 1 -C 4 alkyl groups.
• n-propyl methyl, ethyl, n-propyl, i-propyl, n-butyl and i-butyl or phenyl, ortho- or para-tolyl, para-isopropylphenyl or mesityl.
• Very particularly preferred complexes contain as ligands L 1 triphenylphosphine, tri-C 1 -C 4 alkylphosphine, tritolylphosphine or trimesitylphosphine.
• the groups R 4 and R 5 independently of one another are preferably C 1 -C 4 -alkyl, in particular branched C 1 -C 4 -alkyl, or aryl which may be replaced by 1, 2 or 3 C 1 -C 4 alkyl groups is substituted.
• R 4 and R 5 are particularly preferably independently of one another methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, phenyl, ortho- or para-tolyl, mesityl, ⁇ - or ⁇ -naphthyl. If R 4 and R 5 form a heterocyclic ring together with the P atom to which they are attached, then R 4 and R 5 preferably together represent n-butylene, n-pentylene or 2,2'-biphenylene.
• R 6 represents methyl, ethyl, propyl, i-propyl, n-butyl, 2-butyl, i-butyl, t-butyl, phenyl and benzyl and particularly preferably i-propyl and t-butyl.
• Atoms or groups for R 7 which are preferred according to the invention are hydrogen, methyl or phenyl and particularly preferably hydrogen.
• the absolute configuration of the carbon atoms in the oxazoline part which carry the substituents R 6 and R 7 can be (R) or (S) independently of one another. According to the invention, only those ligands L 2 are suitable in which the configuration on the C atom which carries R 6 is uniform (R) or (S).
• the ligand L 2 is particularly preferably a compound of the formulas (IIIa), (IIIb) or (IIIc) with (R) or (S) configuration on the C atom which bears the alkyl group.
• the ligands L 2 according to the invention are known or can be prepared analogously to known methods. They are prepared, for example, starting from chiral amino alcohols of the general formula (V) by means of an acid catalysis ring closure reaction with o-fluoroaryl nitriles of the general formula (VI) to give the chiral 2- (o-fluoroaryl) oxazoline derivatives of the general formula (VII) (Bolm et al , Chem. Ber. 1991, 124, 1173). These can then be converted with a suitably substituted phosphine anion to the desired ligand L 2 of the general formula (III) (Williamson et al, Synlett, 1993, 509).
• the complexes according to the invention are prepared by reacting a chiral ligand of the general formula (III) with a precursor complex of the formula RuX 1 X 2 L 1 L 2 L 3 , in which X 1 , X 2 and L 1 have the meaning indicated above, L 2 and L 3 are identical or different and are selected from CO, aromatics, which may have 1, 2 or 3 alkyl substituents, in particular p-cymene, dienes, in particular 1,5-cyclooctadiene (COD), or triarylphosphines, in particular triphenylphosphine.
• the ligands L 2 and L 3 may be absent, especially if the precursor complexes are in dimeric or oligomeric form.
• Suitable complexes are, for example, RuCl 2 (PPh 3 ) 3 , [RuCl 2 (p-cymene)] 2 , [RuCl 2 (COD)] x , [RuCl 2 (CO) 3 ] 2 .
• the reaction is carried out in an inert solvent, for example an aromatic which optionally carries 1, 2 or 3 C 1 -C 4 -alkyl substituents or chlorine atoms, preferably benzene, toluene, ethylbenzene, p-cymene, chlorobenzene, dichlorobenzene, or an ether, preferably Diethyl ether, tetrahydrofuran, methyl t-butyl ether, anisole, or a haloalkane, for example dichloromethane, chloroform, dichloroethane, trichloroethane, at temperatures in the range from 0 ° C. to 150 ° C., preferably from 10 ° C. to 100 ° C., particularly preferred at room temperature.
• an inert solvent for example an aromatic which optionally carries 1, 2 or 3 C 1 -C 4 -alkyl substituents or chlorine atoms, preferably benzene, toluen
• R and R ' are prochiral ketones and the transfer hydrogenation catalyzed by the complexes according to the invention to the corresponding alcohols is enantioselective.
• the enantiomeric excess is more than 60% (ee), preferably more than 90% (ee).
• radicals R and R ' There are in principle no restrictions with regard to the type of radicals R and R '. They stand independently of one another for straight-chain or branched alkyl, aryl, (hetero) aryl or (hetero) aralkyl groups, it being possible for all groups in turn to have further groups such as alkyl, (hetero) aryl or (hetero) aralkyl groups.
• One of the radicals R and R ' is preferably an aryl or heteroaryl group.
• the carbonyl function to be reduced can also be built into a mono- or polycyclic ring structure.
• the radicals R and R 'can have functional groups independently of one another.
• the process according to the invention for enantioselective transfer hydrogenation of prochiral ketones is usually carried out by reacting the ketone with a hydrogen donor, preferably a secondary alcohol, in particular i-propanol, 2-butanol, cyclopentanol or cyclohexanol, especially i-propanol, in the presence of catalytic amounts of one or more the complexes according to the invention and catalytic amounts of a base.
• the catalysts are used in amounts of 0.001 to 10 mol% per carbonyl function to be reduced, preferably 0.01 to 1 mol%, in particular 0.05 to 0.5 mol%.
• the amount of base, based on the catalyst, is in the range of 0.5-100 mol equivalents, preferably 1-50 mol-eq., In particular 5-30 mol-eq.
• Suitable bases are alkali metal hydroxides, alkali metal C 1 -C 4 alcoholates, alkali metal hydrides or calcium hydride. Alkali metal hydroxides or alcoholates are preferably used.
• the reaction can be carried out in the secondary alcohol, if it is liquid, as a solvent.
• cosolvents can be used, preferably ethers such as diethyl ether, tetrahydrofuran, methyl t-butyl ether, dioxane, pyran or hydrocarbons, light petroleum fractions, preferably hexane, and chlorinated hydrocarbons, for example dichloromethane or chloroform.
• the reaction is carried out in the range from -30 ° C to 150 ° C, preferably 20 ° C to 100 ° C, and, if the solvent has a lower boiling temperature, under pressure.
• the reaction time is in the range of 15 min. until 12 h.
• the reaction mixture is worked up in a conventional manner, and the product is obtained, for example, by distillation or crystallization.
• a ruthenium complex according to the invention is generated from a suitable ruthenium precursor complex and a ligand L 2 of the general formula (III) in an inert solvent, for example one of the cosolvents mentioned, and then the prochiral ketone, the secondary Alcohol and the base are added and the mixture is reacted.
• the transfer hydrogenation can be carried out using an in situ catalyst prepared from one of Examples 1 to 5 as follows.

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• Chemical Kinetics & Catalysis (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Citations (6)

• 1995
  • 1995-12-22 DE DE19548399A patent/DE19548399A1/de not_active Withdrawn
• 1996
  • 1996-12-05 CA CA002192226A patent/CA2192226C/fr not_active Expired - Fee Related
  • 1996-12-19 DE DE59609005T patent/DE59609005D1/de not_active Expired - Fee Related
  • 1996-12-19 EP EP96120522A patent/EP0780157B1/fr not_active Expired - Lifetime
  • 1996-12-20 US US08/777,743 patent/US5693820A/en not_active Expired - Lifetime
  • 1996-12-24 JP JP35548996A patent/JP3878703B2/ja not_active Expired - Fee Related

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